763 Background: Despite clinical success of VEGF blockade in mCRC, resistance to anti-angiogenic drugs invariably develops. IL-8 and other cytokines have been implicated in resistance development to anti-angiogenic therapy. Levocetirizine is a third generation antihistamine with anti-inflammatory and IL-8 suppression properties. We conducted a phase II trial combining levocetirizine with capecitabine and bevacizumab to potentially overcome anti-angiogenic therapy resistance in patients with refractory mCRC. Methods: This was a single-center open-label prospective trial in refractory mCRC patients. Treatment consisted of oral capecitabine 850mg/m² – 7 days on and 7 days off, IV bevacizumab 5 mg/kg every 14 days and oral levocetirizine 5 mg daily in 14 day cycles. The primary end point was PFS and secondary endpoints included ORR and tolerability. An exploratory endpoint included correlation of PFS with cytokine (IL-8 & IL-6) levels. A sample size of 36 evaluable patients could identify a median PFS of 3.4 months at a 0.05 significance level. To document cytokine changes related to levocetirizine treatment, patients were randomized to Arm A where levocetirizine was started 7 days after starting chemotherapy or to Arm B where levocetirizine was started 7 days prior to chemotherapy. For PFS determination both arms were combined for analysis. Cytokine levels were measured at baseline and with each cycle of chemotherapy (up to three cycles). Results: 43 patients were enrolled in the trial to have 36 evaluable patients. Arm A enrolled 20 patients and Arm B enrolled 23 patients. Of the patients evaluable for best response, 19 had SD and 12 had PD. Median PFS of all patients on the study was 3.4 months (ranging 0.9 to 10.6 months). Conclusions: Median PFS in the trial was comparable to and possibly better than other regimens used in the refractory setting (e.g., median PFS of 1.9 months for regorafenib). Cytokine analysis is in progress and these results and correlations with patient outcomes will be presented to assess the impact of cytokine blockade on mCRC treatment. Clinical trial information: NCT01722162.